Nobel Prizes honor immune work, but include recently deceased winner

This year's Medicine prize goes to work that helped to identify additional …

This year's Noble Prizes in Physiology or Medicine honor researchers who helped identify and characterize previously unknown arms of the immune system. When we think of the immune system, the focus is often on what's called adaptive immunity: the antibodies and cells that are specific to a single pathogen and generate long-term protection. The researchers who were honored with the announcement of the prizes today helped identify a previously unknown system for activating this adaptive response, and discovered what's now termed the innate immune response, a system that's so ancient that it's present in organisms that don't even produce antibodies.

Tragically, it's not clear whether everyone honored in the announcement will eventually be honored with the Prize. The Nobel rules dictate that the award must be granted to a living individual, and one of the intended recipients died three days ago. This is an unprecedented situation, but the organization's board has decided that the Prize will be awarded.

Immunity from flies to man

In 1995, three geneticists who worked on the fruit fly Drosophila won the Physiology or Medicine Nobel, in recognition of the fact that many of the genes that control development also play key roles in human health. One of the pathways that was identified by these researchers controls how the animal develops a distinct back and front. This is termed dorsal-ventral polarity, and is easy to visualize: the wings go on top, legs on the bottom. As the genes in this pathway were cloned (many under the direction of one of my thesis committee members), they fit the pattern that won the Nobel Prize: they fed into a gene that was similar to a human version that had been implicated in the inflammatory immune response.

At the time, this wasn't especially surprising. It has been a long time since flies and vertebrates shared a common ancestor, and evolution frequently repurposes useful genes for new roles. Around the same time the fly work was earning its Noble Prize, however, Jules Hoffmann, of the University of Strasbourg, was looking into how flies responded to pathogens such as fungal infections. One of the genes identified in his work encoded a large protein called Toll—the same protein, it turns out, that sets off the dorsal-ventral pathway. Instead of using an inflammatory pathway for something different, flies had coopted it to control both the development of the organism and an immune response.

A short while later, Bruce Beutler discovered that the system used in flies was also active in humans. Beutler was looking for the genes that mediate a response to a chemical, made by bacteria, that was associated with the onset of septic shock. He used mice that did not respond to septic shock to identify a protein that was key to mediating this response. When the protein was identified, it turned out to be a mammalian version of the Toll protein found in flies.

Since then, a variety of labs have fleshed out a clearer picture of this arm of the immune system. In contrast to the adaptive immune system, which uses many receptors of high specificity (antibodies), the innate immune system uses a limited number of receptors, all related to Drosophila's Toll, that bind to broad classes of molecules that are commonly associated with bacteria or viruses. These include the fat-sugar conjugates that set off septic shock, and the single-stranded RNA that carries the genetic information of many viruses. In mammals, these Toll-like receptors set off an inflammatory response that helps limit the spread of infections.

Immunity under the skin

The other half of the Prize has been given to Ralph Steinman, a Canadian who has been working at Rockefeller University in New York City. Steinman played a key role in identifying a type of immune cell, called a dendritic cell, that's embedded in surfaces that frequently come into contact with the outside world, such as the skin and our breathing passages. The cells had been identified much earlier, but their significance hadn't been recognized.

Through careful experimentation, Steinman was able to show that these cells could play a major role in activating the adaptive immune response, as they helped drive T cells from a resting state to one capable of promoting a full immune response. Further experiments, by Steinman and others, showed that dendritic cells expressed their own specialized form of an immune receptor and could take proteins from invading pathogens and present them to the adaptive immune system for recognition. They also act as a link between the innate immune response and the adaptive form, neatly tying up the themes of this year's Prize into a single package.

Unfortunately, that was the only thing that was neat about Steinman's prize. When the Nobel Committee contacted his home institution to inform them of the honor, a Rockefeller University spokesman conveyed some tragic news: Steinman had died of cancer just three days earlier.

To keep the awards from constantly revisiting the past, the Nobel rules state that the prizes themselves cannot be awarded after a recipient's death. This has only been an issue once before, when a recipient died after the announcement, but before the ceremony in Sweden; that award went ahead. In this case, Steinman had died prior to the announcement of the award, although the Nobel Committee that conferred it to him was unaware of the fact. There's nothing in the rules that covers that particular situation, although strict reading of them would suggest that the Prize should not be given.

Fortunately, the Board of the Nobel Foundation has chosen to recognize the spirit of the rule. The committee that chose Steinman was acting in good faith, and the rule was not meant to strip anyone of an honor due to simple errors. The award will stand.

I'm a little confused. First the article states: "Tragically, it's not clear whether everyone honored in the announcement will eventually be honored with the Prize"

But it then follows up with "but the organization's Board has decided that the Prize will be awarded" and "Fortunately, the Board of the Nobel Foundation has chosen to recognize the spirit of the rule. The committee that chose Steinman was acting in good faith, and the rule was not meant to strip anyone of an honor due to simple errors. The award will stand"

If they've announced it will be awarded, how isn't it clear? Is it likely they'll reverse course?

I'm a little confused. First the article states: "Tragically, it's not clear whether everyone honored in the announcement will eventually be honored with the Prize"

But it then follows up with "but the organization's Board has decided that the Prize will be awarded" and "Fortunately, the Board of the Nobel Foundation has chosen to recognize the spirit of the rule. The committee that chose Steinman was acting in good faith, and the rule was not meant to strip anyone of an honor due to simple errors. The award will stand"

If they've announced it will be awarded, how isn't it clear? Is it likely they'll reverse course?

Sorry, the announcement came out as i was writing it. I thought I managed to retweak everything, but it seems i missed a bit. Will fix that now.

I think it's the right decision, They had intended to give the prize to a living person. Only after their decision had been made was it discovered that he had sadly passed away.

I think the fact that it was only 3 days is irrelevant, the fact that they had genuinely believed that the person to be honoured was still alive, and in fact was still alive when they started to select their candidates was the biggest factor. They weren't knowingly trying to award someone who was already deceased, or had died six months prior to the selection process (a couple of months would probably be more than enough time for the news to have reached them).

I'm a little confused. First the article states: "Tragically, it's not clear whether everyone honored in the announcement will eventually be honored with the Prize"

But it then follows up with "but the organization's Board has decided that the Prize will be awarded" and "Fortunately, the Board of the Nobel Foundation has chosen to recognize the spirit of the rule. The committee that chose Steinman was acting in good faith, and the rule was not meant to strip anyone of an honor due to simple errors. The award will stand"

If they've announced it will be awarded, how isn't it clear? Is it likely they'll reverse course?

Sorry, the announcement came out as i was writing it. I thought I managed to retweak everything, but it seems i missed a bit. Will fix that now.

Ah, good, I was hoping it was something like that. Thanks for the follow-up.

I disagree with the posthumous awarding. One of the reasons it is given to living recipients is that it gives them money to further fund their research or peace movements. Awarding the prize to dead laureates would be, to be honest, a waste of money better spent on still-viable researchers.

I disagree with the posthumous awarding. One of the reasons it is given to living recipients is that it gives them money to further fund their research or peace movements. Awarding the prize to dead laureates would be, to be honest, a waste of money better spent on still-viable researchers.

If he were the only winner this year I would agree, but the actual honor can be bestowed while the award funds go to living researchers

Is this the same committee that gave Obama the Nobel for doing nothing more than a few speeches (which he didn't write) and empty promises, *after* the deadline for consideration had expired? That was a violation of the rules too, and has to be a low point in the Nobel's history.

Is this the same committee that gave Obama the Nobel for doing nothing more than a few speeches (which he didn't write) and empty promises, *after* the deadline for consideration had expired? That was a violation of the rules too, and has to be a low point in the Nobel's history.

No. The Nobel prizes are selected by different committees of experts in the required field.The Medical prize is selected by Karolinska Institutet in Sweden, while the peace prize is awarded by the norwegian parliament.

I disagree with the posthumous awarding. One of the reasons it is given to living recipients is that it gives them money to further fund their research or peace movements. Awarding the prize to dead laureates would be, to be honest, a waste of money better spent on still-viable researchers.

That might make sense if the Nobel committee tended to award prizes in a timely manner, so that the recipient was still active and productive. It often does not. Even if Steinman were still alive, he would be 68 years old, past the point when most people do their best work. The extreme case is probably that of Peyton Rous who was awarded the prize 55 years after the discovery for which he received it. He was in his late 80's at that point.

I disagree with the posthumous awarding. One of the reasons it is given to living recipients is that it gives them money to further fund their research or peace movements. Awarding the prize to dead laureates would be, to be honest, a waste of money better spent on still-viable researchers.

That might make sense if the Nobel committee tended to award prizes in a timely manner, so that the recipient was still active and productive. It often does not. Even if Steinman were still alive, he would be 68 years old, past the point when most people do their best work. The extreme case is probably that of Peyton Rous who was awarded the prize 55 years after the discovery for which he received it. He was in his late 80's at that point.

Besides the time lag, no one who is worthy of consideration for a (scientific) Nobel is in any need of funding. It's not like the Nobel committee is finding hidden gems of research--the stuff that wins these prizes is already widely recognized as being incredibly significant, and the researchers involved are thus quite well-established.